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Title: Molecular and virological analysis of HIV-associated persistent generalised lymphadenopathy (PGL)
Author: Reddy, Archana
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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Approximately one-third of HIV-infected individuals present early in infection with a syndrome called Persistent generalised lymphadenopathy (PGL). The enlarged lymph nodes of this condition may represent pre-malignant lesions. The aim of this study was to identify early genetic lesions that might be predictive of future lymphoma development in these individuals. Lymph node biopsies from 23 individuals with PGL were analysed for alterations in the structure and expression of selected genes. Reactive lymph node and tonsil controls from HIV-uninfected individuals served as controls. The results of the study were as follows: i) Mutations in p53 were detected in 26% of HIV-infected individuals. ii) A distinct pattern of p73 and p63 gene expression was observed in the HIV-PGL samples when compared with the uninfected lymph node and tonsil controls. iii) Structural modifications of the genes on the INK4 locus were absent iv) Epigenetic silencing of the INK4a, INK4b, p73 and death-associated protein kinase (DAPK) genes by hypermethylation was not observed. v) Mutations in bcl-6 were detected in 26% of HIV-infected individuals and in 12.5% of healthy individuals, along with polymorphic substitutions at nucleotides, +753 and +875. vi) Rearrangements of c-myc t(8:14) and bcl-2 t(14:18) was not observed in either the study or control groups except for a single t(8:14) in the lymph node of a healthy individual. vii) EBV DNA was detected in 100% of HIV-infected individuals and in 86% of healthy individuals KSHV DNA was detected in 8.7% of HIV-infected individuals and in none of the healthy controls. Based on the findings in this study, a partial model for the molecular pathogenesis of AIDS-NHL is a proposed: p53 and bcl-6 mutations occur early in lymphomagenesis, whereas activation/deregulation of oncogenes such as c-myc and bcl-2, and/or inactivation of the tumour suppressor genes of the INK4 family, do not constitute early phenomena in the development of AIDS-NHL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available